The dienoic condensation or cycloaddition 4.pi.+2.pi.!, which is also known as the Diels-Alder reaction, is the most important method for synthesizing hexacyclic structures. It consists in thermally reacting a diene that is conjugated on a dienophile, which can be the diene itself, another diene or a monoene, resulting in a 1:1 adduct. When the reactivity of the diene or the dienophile is low, it is necessary to operate at high temperature; this often leads to undesirable polymerization reactions of the diene or polyaddition of the adduit. By contrast, the regioselectivity, diastereofacial selectivity, and the cis/trans ratio of the condensation are fixed and do not always correspond to the product that is sought.
For this reason, it has been proposed that organic solvents be used to improve the speed, regioselectivity, and stereoselectivity of these reactions. In addition to the fact that the effect of these solvents is relatively limited, however, their use poses the problem of separating them from reagents and products.
It has also been proposed to implement the Diels-Alder reaction in the presence of water. The effect of water, or water-rich aqueous alcohol solutions, on the reaction speed is often significant. Furthermore, the endo/exo ratio is always higher there than in the organic medium. The presence in the water of mineral salts, such as lithium salts, further accelerates the reaction.
Furthermore, it has been shown that the Lewis acids, such as TiCl.sub.4, BF.sub.3 or AlEtCl.sub.2, and their alkoxy substitutes, and various cationic complexes of transition metals with acid properties enhance the reaction and its stereoselectivity. In this case, the reaction can be considered as catalyzed. The presence of optically active groups in these compounds also makes it possible to induce a catalytic enantioselective reaction.
All of these effects have been discussed in articles published in Chemical Reviews by U. Pindur and Associates, Vol. 93, p. 741, and by H. Kagan and O. Riant, Vol. 92, p. 1007.
Very recently, J. Engberts and Associates showed in an article in the Journal of the American Chemical Society, Vol. 118, p. 7702, that the combined effect of water and certain weak Lewis acids such as the nitrates of Co, Cu, Ni and Zn made it possible to carry out at ambient temperature Diels-Alder reactions with fairly unreactive dienophiles, and to do so at significant speeds. In contrast, the growing endo/exo ratio observed in pure water disappeared in the presence of a Lewis acid.